Feedback control of ultrafiltration to prevent hypotension

ABSTRACT

A method and system for the extracorporeal treatment of blood to remove fluid from the fluid overloaded patient is disclosed that non-invasively measures an oxygen level in the venous blood. The oxygen blood level is used to detect when hypotension is about to occur in a patient. The oxygen level measurements are used as feedback signals. These feedback signals are applied to automatically control the rate of fluid extraction to achieve the desired clinical outcome and avoid precipitating a hypotensive crisis in the patient.

FIELD OF INVENTION

[0001] The present invention relates to an apparatus for theextracorporeal treatment of blood and more specifically to the automaticcontrol of fluid removal from the blood of patients suffering from fluidoverload and averting therapy induced hypotension.

BACKGROUND OF THE INVENTION

[0002] Renal Replacement Therapy (RRT) has evolved from the long, slowhemodialysis treatment regime of the 1960's to a diverse set of therapyoptions, the vast majority of which employ high permeability membranedevices and ultrafiltration control systems.

[0003] Biologic kidneys remove metabolic waste products, other toxins,and excess water. They also maintain electrolyte balance and produceseveral hormones for a human or other mammalian body. An artificialkidney, also called a hemodialyzer or dialyzer, and attendant equipmentand supplies are designed to replace the blood-cleansing functions ofthe biologic kidney. At the center of artificial kidney design is asemipermeable filter membrane that allows passage of water,electrolytes, and solute toxins to be removed from the blood. Themembrane retains in the blood, the blood cells, plasma proteins andother larger elements of the blood.

[0004] Over the last 15 years, the intended use of the RRT equipment thesystem has evolved into a subset of treatment alternatives that aretailored to individual patient needs. They include ultrafiltration,hemodialysis, hemofiltration, and hemodiafiltration, all of which aredelivered in a renal care environment, as well as hemoconcentration,which is typically delivered in open heart surgery. Renal replacementtherapies may be performed either intermittently or continuously, in theacute or chronic renal setting, depending on the individual patient'sneeds.

[0005] Ultrafiltration involves the removal of excess fluid from thepatient's blood by employing a pressure gradient across a semipermeablemembrane of a high permeability hemofilter or dialyzer. For example,removal of excess fluid occurs in hemoconcentration at the conclusion ofcardiopulmonary bypass surgery. Hemodialysis involves the removal oftoxins from the patient's blood by employing diffusive transport throughthe semipermeable membrane, and requires an electrolyte solution(dialysate) flowing on the opposite side of the membrane to create aconcentration gradient. A goal of dialysis is the removal of waste,toxic substances, and/or excess water from the patients'blood. Dialysispatients require removal of excess water from their blood because theylack the ability to rid their bodies of fluid through the normal urinaryfunction.

[0006] One of the potential risks to health associated with RRT ishypotension, which is an abnormal decrease in the patient's bloodpressure. An abnormally high or uncontrolled ultrafiltration rate mayresult in hypovolemic shock, hypotension, or both. If too much water isremoved from the patient's blood, such as might occur if theultrafiltration rate is too high or uncontrolled, the patient couldsuffer hypotension and/or go into hypovolemic shock. Accordingly, RRTtreatments must be controlled to prevent hypotension.

[0007] Alternatively, a patient may experience fluid overload in hisblood, as a result of fluid infusion therapy or hyperalimentationtherapy. Certain kinds of RRT machine failures may result in fluid gainrather than fluid loss. Specifically, inverse ultrafiltration may resultin unintended weight gain of a patient and is potentially hazardous.Uncontrolled infusion of fluid by whatever mechanism into the patientcould result in fluid overload, with the most serious acute complicationbeing pulmonary edema. These risks are similar in all acute and chronicrenal replacement therapies (ultrafiltration, hemodialysis,hemofiltration, hemodiafiltration, hemoconcentration). Monitoringpatients to detect excessive fluid loss is needed to avoid hypotension.

[0008] Rapid reduction in plasma or blood volume due to excessiveultrafiltration of water from blood may cause a patient to exhibit oneor more of the following symptoms: hypovolemia-hypotension, diaphoresis,cramps, nausea, or vomiting. During treatment, plasma volume in thepatient's blood would theoretically remain constant if the plasmarefilling rate equaled the UF (ultrafiltration) rate. However, refillingof the plasma is often not completed during a RRT session. The delay inrefilling the plasma can lead to insufficient blood volume in a patient.

[0009] There appears to be a “critical” blood volume value below whichpatients begin to have problems associated with hypovolemia (abnormallydecreased blood volume). Fluid replenishing rate is the rate at whichthe fluid (water and electrolytes) can be recruited from tissue into theblood stream across permeable walls of capillaries. This way bloodvolume is maintained relatively constant. Most of patients can recruitfluid at the rate of 500 to 1000 mL/hour. When patients are treated at afaster fluid removal rate, they begin to experience symptomatichypotension.

[0010] Hypotension is the manifestation of hypovolemia or a severe fluidmisbalance. Symptomatically, hypotension may be experienced by thepatient first as light-headedness. To monitor patients for hypotension,non-invasive blood pressure monitors (NIBP) are commonly used duringRRT. When detected early, hypotension resulting from the excessive lossof fluid is easily reversed by giving the patient intravenous fluids.Following administering fluids the RRT operator can adjust theultrafiltration rate to make the RRT treatment less aggressive.

[0011] Ultrafiltration controllers were developed specifically to reducethe occurrence of hypotension in dialysis patients. Ultrafiltrationcontrollers can be based on approximation from the known trans-membranepressure (TMP), volume based or gravity based. Roller pumps and weightscales are used in the latter to meter fluids. Ultrafiltrationcontrollers ensure the rate of fluid removal from a patient's blood isclose to the fluid removal setting that was selected by the operator.However, these controllers do not always protect the patient fromhypotension. For example, the operator may set the fluid removal ratetoo high. If the operator setting is higher than the patient's fluidreplenishing rate, the operator should reduce the rate setting when thesigns of hypotension manifest. If the excessive rate is not reduced, thepatient may still suffer from hypotension, even while the controlleroperates properly.

[0012] Attempts were made during the last two decades to developmonitors that could be used for feedback control of dialysis machineparameters, such as dialysate concentration, temperature, andultrafiltration rate and ultrafiltrate volume. Blood volume feedbacksignals have been proposed that are based on optical measurements ofhematocrit, blood viscosity and blood conductivity. Real time controldevices have been proposed that adjust the ultrafiltration rate tomaintain the blood volume constant, and thereby balance the fluidremoval and fluid recruitment rates. None of these proposed designs ledto significant commercialization owing to the high cost of sensors, highnoise to signal ratio or lack of economic incentive for manufacturers.In addition, many of these proposed systems required monitoring ofpatients by highly trained personnel.

[0013] Controllers that protect from hypotension are especially neededfor patients suffering from fluid overload due to chronic CongestiveHeart Failure (CHF). In CHF patients, fluid overload typically is notaccompanied by renal failure. In these patients mechanical solute(toxins) removal is not required. Only fluid (plasma water) removal isneeded. Ideal Renal Replacement Therapy (RRT) for these patients is SlowContinuous Ultrafiltration (SCUF) also known as “Ultrafiltration withoutDialysis”.

[0014] SCUF must be controlled to avoid inducing hypotension in thepatient. Due to their poor heart condition, CHF patients are especiallyvulnerable to hypotension from excessively fast fluid removal. Theclinical treatment objective for these patients can be formulated as:fluid removal at the maximum rate obtainable without the risk ofhypotension. This maximum rate is equivalent to fluid removal at themaximum rate at which the vascular volume can be refilled from tissue.This maximum rate for CHF patients is typically in the 100 to 1,000mL/hour range. The rate can vary with the patient's condition and isalmost impossible to predict. The rate can also change over the courseof treatment, especially if the objective of treatment is to remove 2 to10 liters of fluid.

[0015] Hypotension in CHF patients often results from a decrease of thecardiac output of the patient. Cardiac output is the volume of bloodthat is ejected per minute from the heart as a result of heartcontractions. The heart pumps approximately 4-8 L/min in a normalperson. In a CHF patient cardiac output most often decreases because theheart is subject to a reduction of filling pressure. This dependency onthe filling pressure is a well-known clinical consequence of thedeterioration of the heart muscle during CHF. In a healthy person whenthe heart filling pressure is lowed, the heart will compensate andmaintain cardiac output by working (e.g. pumping) harder. Fillingpressure is the blood pressure in the right atrium of the heart. Thispressure is approximately equal to the patient's venous pressuremeasured elsewhere in a great or central vein (such as vena cava) andcorrected for gravity. In a fluid overloaded CHF patient Central VenousPressure (CVP) is typically between 10 and 20 mmHg. If this pressuredrops by 5 to 10 mmHg, the patient is likely to become hypotensive soon.

[0016] The danger of hypotension as a consequence of excessive fluidremoval during dialysis and other extracorporeal blood treatments hasbeen recognized. U.S. Pat. No. 5,346,472 describes a control system toprevent hypotension that automatically adjusts the sodium concentrationadded to the dialysate by infusing a hypertonic or isotonic salinesolution in response to operator input or patient's request based onsymptoms. European patent EU 0311709 to Levin and Zasuwa describesautomatic ultrafiltration feedback based on arterial blood pressure andheart rate. U.S. Pat. No. 4,710,164 describes an automaticultrafiltration feedback device based on arterial blood pressure andheart rate. U.S. Pat. No. 4,466,804 describes an extracorporealcirculation system with a blood oxygenator that manipulates thewithdrawal of blood to maintain CVP constant. U.S. Pat. No. 5,938,938describes an automatic dialysis machine that controls ultrafiltrationrate based on weight loss or the calculated blood volume change. Latemodel AK200 dialysis machines from Gambro (Sweden) include an optionalblood volume monitor called BVS or Blood Volume Sensor. This sensor isoptical and in fact measures blood hematocrit or the concentration ofred blood cells in blood. Since dialysis filter membranes areimpermeable to blood cells, increased hematocrit signifies the reductionof the overall blood volume. The BVS sensor is not included in afeedback to the machine and is used to help the operator assess the rateof fluid removal.

[0017] U.S. Pat. No. 5,346,472 describes a mixed venous oxygensaturation responsive system for treating a malfunctioning heart. Bysensing the change of the oxygen content in the venous blood the systemadjusts the operation of a heart pacemaker. However, venous saturationof blood has never been used in adjusting an extracorporeal bloodtherapy for fluid removal such as ultrafiltration, hemofiltration ordialysis.

[0018] Other devices have been proposed that use arterial pressure as afeedback to the ultrafiltration controller to avoid hypotension.Automatic Non-Invasive Blood Pressure (NIBP) monitor feedback was usedas a control system input. NIBP measures systolic and diastolic arterialblood pressure by periodically inflating a blood pressure cuff aroundthe patient's arm or leg. Acoustic or oscillatory methods detect thepressure level at which blood vessels collapse.

[0019] This level approximates systemic arterial blood pressure. Closedloop dialysis or fluid removal devices designed around this principlehave several inherent deficiencies, including:

[0020] a) NIBP is inaccurate. Errors of up to 20 mmHg can be expected inthe system. To avoid system oscillations and false alarms, the feedbackwould have to be slow and heavily filtered.

[0021] b) NIBP is not continuous, but is rather based on periodicpressure measurements. If the blood pressure cuff were inflated morefrequently, less than every 15 minutes a patient would experiencesignificant discomfort. Also, blood vessels change their elasticity fromthe frequent compressions of the blood cuff. This change in elasticitycan add to the inaccuracy of cuff pressure measurements.

[0022] c) The arterial pressure in a CHF patient does not dropimmediately following the reduction of cardiac output. It may takeconsiderable time for a CHF patient to exhaust their cardiac reserve. Bythat time, the hypotension would have already occurred and its reversalwould require medical intervention. Accordingly, hypotension may occurbefore NIBP detects it.

[0023] d) In a CHF patient, arterial blood pressure is maintained by thebody to protect the brain. Neurohormonal signals are sent in response tobaroreceptors that cause vasoconstriction of blood vessels to legs,intestine and kidneys. By sacrificing other body organs needs, arterialblood pressure to the brain can be kept constant at the expense ofreduced blood flow to organs while the cardiac output is reduceddramatically.

[0024] Altogether, hypotension in a CHF patient can create a dangeroussituation when the arterial blood pressure is apparently normal, whilethe overall condition of the patient is worsening. By the time the NIBPmeasurement has detected hypotension, serious medical intervention maybe needed.

[0025] It is desired to have a feedback based control system that willcontinuously and automatically manipulate the ultrafiltration rate toachieve optimal ultrafiltration. In such a system, fluid is removedrapidly and without the risk of hypotension. It is also desired, in theapplication to CHF patients, to anticipate and correct the onset of thecondition that before it is manifested by the reduction of arterialpressure.

SUMMARY OF INVENTION

[0026] A method and system has been developed for removing fluid from afluid overloaded patient at a maximum safe rate that does not requirehuman monitoring and interaction. The system senses oxygen saturation ina patient's venous blood as being indicative of conditions that causehypotension. By monitoring oxygen saturation, the system detects thedecrease of cardiac output that precedes the onset of hypotension andmaintains a safe filtration rate by reducing or periodically turning offultrafiltration when the oxygen saturation feedback signal indicatesthat hypotension may occur. Using the system that has an oxygensaturation feedback signal, hypotension is averted before it occurs.

[0027] A real time feedback system has been developed that:

[0028] a) Allows for an optimal rate of fluid removal in vulnerable CHFpatients by automatically measuring and monitoring venous blood oxygenlevel, e.g., SvO₂, as indicators of the potential of hypotension.

[0029] b) Prevents episodes of hypotension so that fluid removaltreatment can be conducted under minimal supervision.

[0030] c) Uses robust and inexpensive measurement system for monitoringthe physiological blood parameters.

[0031] A method and system has been developed for removing fluid from afluid overloaded patient at a maximum safe rate that does not requirehuman monitoring and interaction to avoid hypotension. The system uses aphysiologic blood variable, such as the oxygen level in blood, as beingindicative of conditions that cause hypotension. The system maintainsthe physiological variable at a safe level by reducing or periodicallyturning off ultrafiltration. In this way hypotension is averted beforeit occurs.

[0032] In some instances, the absolute value of a physiologic bloodvariable or its significance is difficult to determine accurately.However, the change of the variable may be accurately determined, evenif the absolute value of the variable is difficult to measure. Duringultrafiltration treatment, the amount of change in a variable may bedetermined from a level of the variable established at the beginning oftreatment. For example, a 20% drop of cardiac output during treatment iseasier to detect than determining an absolute value for cardiac outputor an absolute cardiac output value that is indicative of insufficientoutput. In particular, detecting a substantial drop of 20% in cardiacoutput may be more readily determined, than detecting when cardiacoutput falls below a 3 liter/minute threshold. Thus, an amount ofchange, rate of change and/or percentage change in a physiological bloodparameter may be used to detect hypotension.

[0033] Mixed Venus Oxygen Saturation (SvO₂) provides a good estimate ofthe metabolic oxygen supply and demand and is related to cardiac output.When the cardiac output is decreased or when the cardiac output cannotcompensate for increased oxygen utilization, the mixed venous oxygencontent falls. SvO₂ represents the end result of both oxygen deliveryand consumption at the tissue level for the entire body. Clinically,SvO₂ can be the earliest indicator of acute deterioration and is closelyrelated to cardiac output. Venous blood is normally relativelyunoxygenated, having not yet traveled through the lungs, with asaturation of 60-80%. The level of SvO₂ is a function of how much oxygenis being extracted from the blood by the organs. SvO₂ is an indicator ofthe supply and demand of oxygen to the tissues.

[0034] Arterial oxygen delivery is the product of cardiac output (QT)and arterial oxygen content (Cao₂); a reduction in either QT or Cao₂threatens the adequacy of oxygen delivery. In either case (reduced QT orreduced CaO2), lactic acidosis and death will ensue if tissue oxygenuptake (Vo₂) is not maintained by the product of QT times the(Cao₂-Cvo₂). When cardiac output is decreased or when cardiac outputcannot compensate for a decrease in Cao₂, the mixed venous oxygencontent (and thus SvO₂ and Pvo₂) will fall. Thus, SvO₂ is a barometer ofthe adequacy of oxygen delivery (QT×Cao₂) for the body's oxygen needs.

[0035] During RRT treatment of a fluid overloaded patient, SvO₂ shouldremain within normal ranges, and change very little. Hemoglobin contentand oxygen consumption should vary only slightly during the 4-8 hour oftreatment for fluid overload. A sudden decrease of SvO₂ is most likelyan indication of sudden drop of cardiac output and a precursor ofhypotension. Accordingly, detecting a substantial change in SvO₂ levelscan be used as an indicator of hypotension and used to reduce a bloodtreatment rate, such as an ultrafiltration rate.

[0036] Venous blood oxygen saturation is an accepted indicator of theremaining oxygen content in the venous blood. Hemoglobin (Hb), anintracellular protein, is the primary vehicle for transporting oxygen inthe blood. Hemoglobin is contained in erythrocytes, more commonlyreferred to as red blood cells. Oxygen is also carried (dissolved) inplasma, but to a much lesser degree. Under conditions of increasedoxygen utilization by the tissues, oxygen that is bound to thehemoglobin is released into body tissue. When the patient inhales,oxygen from the air is absorbed in the blood, as the blood passesthrough lungs. Each hemoglobin molecule in the blood has a limitedcapacity to bond to oxygen molecules. Oxygen saturation is the degree towhich the capacity to bind to oxygen is actually filled by oxygen boundto the hemoglobin. Oxygen saturation, when expressed as a percentage, isthe ratio of the amount of oxygen molecules bound to the hemoglobin, tothe oxygen carrying capacity of the hemoglobin. The oxygen carryingcapacity is determined by the amount of hemoglobin present in the blood.

[0037] Moreover, SvO₂ changes can be measured non-invasively using pulseoxymetry. Non-invasive photoelectric pulse oximetry has been previouslydescribed in U.S. Pat. Nos. 4,407,290, 4,266,554, 4,086,915, 3,998,550and 3,704,706. Pulse oxymeters are commercially available from NellcorIncorporated, Pleasanton, Calif., U.S.A., and other companies forintegration in medical devices.

[0038] Pulse oxymeters typically measure and display various blood flowcharacteristics including but not limited to blood oxygen saturation ofhemoglobin in arterial blood. The oxymeters pass light through human oranimal body tissue where blood perfuses the tissue such as a finger, anear, the nasal septum or the scalp, and photoelectrically sense theabsorption of light in the tissue. The amount of light absorbed is thenused to calculate the amount of blood constituent being measured. Thelight passed through the tissue is selected to be of one or morewavelengths that is absorbed by the blood in an amount representative ofthe amount of the blood constituent present in the blood. The amount oftransmitted light passed through the tissue will vary in accordance withthe changing amount of blood constituent in the tissue and the relatedlight absorption.

[0039] For example, the Nellcor N-100 oximeter is a microprocessorcontrolled device that measures oxygen saturation of hemoglobin usinglight from two light emitting diodes (“LED's”), one having a discretefrequency of about 660 nanometers in the red light range and the otherhaving a discrete frequency of about 925 nanometers in the infraredrange.

[0040] Since in a RRT machine blood circulates outside of the bodythrough a transparent plastic tube, the photometric method of oximetrycan be easily adapted for the application. Light emitting LED's and thelight receiving device can be placed on the opposite sides of the tube.Device can be calibrated to subtract the affects of the tubing on themeasurement.

[0041] During the fluid removal treatment in a CHF patient, centralvenous blood is not always available. In some cases in acute RRTtreatment so called central venous catheters are used for bloodwithdrawal and return. These catheters are advanced from a femoral,jugular or subclavian veins. The tip of the catheter is advanced deepinto the body until central access to venous blood is established. Suchcatheters can draw true mixed venous blood similar in composition to theblood in the right atrium of the heart. Such catheters are associatedwith high risks that are not always acceptable.

[0042] It is desired to have a device for treatment of fluid overloadedCHF patients that will only draw blood from a peripheral vein that isalways available. Suitable peripheral veins are the veins in the arm ofthe patient. The tip of the catheter can be located in a relativelysmall vein in the middle of the arm or could be advanced close to theshoulder. In the latter case, if the tip has past venous valves, theblood in the extracorporeal circuit will be similar in composition tothe blood in a central vein. Although oxygen saturation in the bloodfrom a peripheral vein reflects both global and local organ oxygenextraction, and can be used to detect low cardiac output based onmeasurements of SvO₂. Accordingly, SvO₂ changes can be monitored duringblood treatments that use central, mid line (closer to the shoulder) andperipheral blood access.

BRIEF DESCRIPTION OF THE DRAWINGS

[0043] The attached drawings and associated written description disclosean exemplary embodiment of the present invention:

[0044]FIG. 1 shows a high level schematic diagram of an ultrafiltrationsystem that detects oxygen level in the blood.

[0045]FIG. 2 illustrates a non-invasive sensor system for measuringvenous oxygen saturation in a blood filled tube by optical oximetry.

[0046]FIG. 3 shows a curve of venous oxygen saturation measurements overtime during a course of fluid extraction therapy in a fluid overloadedpatient undergoing fluid removal.

[0047]FIG. 4 shows a curve of venous oxygen saturation expressed as apercentage of the baseline value.

[0048]FIG. 5 illustrates a method of controlling ultrafiltration byestablishing a predetermined deviation from baseline value of oxygensaturation.

[0049]FIG. 6 illustrates design of the controller for ultrafiltrationapparatus.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0050]FIG. 1 shows a high level schematic diagram of an ultrafiltrationsystem, such as is disclosed in commonly-owned U.S. Pat. No. ______(U.S. patent application Ser. No. 09/660,195 (attny.dkt. 3659-17), filedSep. 12, 2000), entitled “Blood Pump Having A Disposable Blood PassageCartridge With Integrated Pressure Sensor”, and U.S. Pat. No. ______(U.S. patent application Ser. No. ______ (attny.dkt. 3659-18), filedSep. 12, 2000), entitled “Method And Apparatus For Blood Withdrawal AndInfusion Using A Pressure Controller” and filed Nov. 2, 2000, both ofwhich applications are incorporated by reference in their entirety.

[0051] Blood is withdrawn from the vein 103 of a human or othermammalian patient using a withdrawal needle 105. The blood flows fromthe needle into a withdrawal bloodline 106 that is equipped with anin-line pressure sensor 107. The sensor transmits a signal indicative ofthe blood pressure in the withdrawal line to a computer controller 110.The withdrawal line loops through a blood pump 108. The pump creates asuction (negative) pressure in the withdrawal line that draws blood fromthe vein and into the line.

[0052] The pump also forces blood through a filter 111 that removesexcess fluid from the blood. The filter includes a blood passage coupledbetween a blood inlet and outlet to the filter, a filtering membraneforming a portion of the walls of the passage, and a filtered fluidoutlet section on a opposite side of the membrane from the bloodpassage. The membrane is pervious to fluids, but not to blood cells andrelatively large solutes in the blood.

[0053] Some percentage of fluid (usually 10 to 20%) in the blood flowingthrough the blood passage in the filter may pass through the membrane tothe outlet section and thereby be filtered from the blood. However, theblood cells and larger proteins in the blood do not pass through thefilter membrane and remain in the blood as it exits the filter. Thefilter has a blood outlet connected to a return line 113 through whichflows blood to be infused back into a vein 102 of the patient. Thefilter has a second output through which flows separated ultrafiltrate(plasma water) that passes in a filtrate line that loops through ametering pump 114 and into a collection bag 116.

[0054] The ultrafiltrate pump 114 is capable of generating a negativepressure in the filtrate line (and at the output side of the filtermembrane) to assist the flux of ultrafiltrate across the membrane, whichhas a substantial hydraulic resistance. The pressure level in thefiltrate line and in the filtrate output section of the filter isdetermined by the rotational speed of the ultrafiltrate pump 114. Therotational speed of pumps 108 and 114 is determined by a controller 110that can be a microcomputer. The controller receives pressuremeasurements from blood line return sensor 112 and the ultrafiltratepump sensor 119. The controller is programmed to adjust theultrafiltrate pump speed to provide a pressure level in the filtrateline to achieve a desired filtration rate. An oxygen sensor 109 isincorporated in the blood tubing 106 prior to the blood pump 108. Signalfrom the sensor 109 is communicated to the controller 110.

[0055] Generally, just prior to the ultrafiltration treatment, anoperator, such as a nurse or medical technician, selects certain controlsettings on the controller for the treatment. The settings (which may beselected by the operator or preprogrammed into the controller, or acombination of both) may include (among other settings) a desired fluidremoval rate from the blood. This rate may be applied by the controllerto determine the rotational speed of the ultrafiltration pump 114.

[0056] The rotational speed of the pump 114 controls the pressure(measured by ultrafiltrate sensor 109) in the output section of thefilter. The fluid pressure in the output section is present on one sideof the filter membrane. The fluid pressure of the blood in the bloodpassage is present on the other side of the membrane. The filtrationrate is dependent on the pressure difference across the membrane of thefilter. The filtration rate is controlled by the pressure in thefiltrate outlet section of the filter, assuming that the blood pressurein the filter blood pressure remains constant. Accordingly, thefiltration rate is controlled by the speed of the ultrafiltration pump114 which determines the fluid pressure in the filter outlet section.

[0057] A safety feature of the controller is that it adjusts thefiltration rate to avoid hypotension of the patient. If too much fluidis removed too rapidly from the blood of the patient, the patient maysuffer from hypotension. To avoid hypotension, the controller monitors afeedback signal from the sensor 109 that detects oxygen saturation inthe blood. The signal from the sensor 109 is continuously evaluated todetermine whether the patient is at risk of suffering hypotension and,if so, reducing the ultrafiltration rate or temporarily interruptingultrafiltration.

[0058] The controller 110 controls the rate of fluid removal from theblood by modifying the rotational speed of the ultrafiltrate pump 114.Control can be exercised by slowly adjusting the rotational speed of thepump 114 with a closed loop controller or by stopping it altogetheruntil the venous volume is refilled. Alternatively, the controller maycyclically stop and start the ultrafiltration pump in a sequence of dutycycles. During a duty cycle, the pump is ON during a portion of eachcycle and is OFF during the remainder of the cycle. The portion of theduty cycle during which pump 114 is ON versus OFF determines thefiltration rate. Other methods for controlling fluid removal includeperiodically clamping the ultrafiltrate line to block the output of thefilter and prevent fluids from being removed from blood in the filter.

[0059] The saturation of oxygen in the blood can be measured by anon-invasive means of oximetry since, during the ultrafiltration, venousblood is passed through the extracorporeal circuit. FIG. 2 shows thevenous blood 202 passing through the plastic tube 203 with a transparentwall. The biosensor consists of a photo emitter 204 and a photo receiver201. The emitter may be a light diode emitting light at a particularwavelength. The photo receiver is coupled with a digital signalprocessing (DSP) unit in the controller capable of extracting theinformation about oxygen saturation by the means well known in the fieldof pulse oximetry. Products for photometric pulse oximetry are availablefrom several manufactures and are well suited for detecting oxygenconcentration in a bloodline.

[0060]FIG. 3 is a chart showing venous oxygen saturation as a functionof time for a fluid overloaded patient undergoing fluid removaltreatment. If the fluid removal rate exceeds the refilling rate, thecardiac output will be reduced. Since oxygen extraction stays the same,the SvO₂ line 301 declines gradually from 60% saturation. When the linecrosses the allowed threshold 302, ultrafiltration is stopped by thecontroller which is monitoring SvO₂ level based on the optical bloodoxygen sensor. With the ultrafiltration being stopped, the vascularvolume is gradually refilled, and consequently, the heart fillingpressure is increased, as is cardiac output. At point 303, the processis reversed and the SvO₂ starts to increase. Since point 304 is abovethe preset threshold, ultrafiltration is safely and automaticallyrestarted by the controller.

[0061]FIG. 4 illustrates controlling ultrafiltration using the relativechange of a physiologic parameter such as SvO₂. At the beginning oftreatment 401, a baseline value is established for the physiologicparameter to be monitored. The baseline value is expressed as 100% inthe chart shown in FIG. 4. The operator determines what percentagedeviation from the baseline is allowed. In this example, a range 407 isset to 7% of baseline. The treatment is started. If in the course oftreatment 402 parameter falls below 93% of the baseline ultrafiltrationis stopped (or the ultrafiltration rate is slowed) until the conditionis restored 403. Once safe condition is restored, treatment continues.

[0062]FIG. 5 illustrates an algorithm used by the ultrafiltrationcontroller with an oxygen saturation feedback. The calculations forcontrolling the flow through the pump 114 are made in thecomputer—controller 110. The controller receives input from the operator118 such as a flow rate setting. The operator may enter the desiredinitial rate of fluid removal or the allowed tolerances to the change ofthe oxygen saturation of venous blood measured by sensor 109. At thebeginning of treatment, a baseline value 501 of SvO₂ is established andstored in the computer memory. Periodically the controller measures thereading 502 of the sensor 109. Next, a deviation 503 of the reading fromthe stored baseline is calculated and compared 504 to the allowed limit.If the deviation exceeds the allowed amount, the fluid removal rate 505is recalculated and the rotational speed 506 of the ultrafiltrate pump114 is reduced by the predetermined amount (controller gain). Unless theend of treatment time 507 is reached, the process is repeated startingfrom an updated measurement 502 of oxygen in blood. More sophisticatedalgorithms can be employed if the slow continuous control of fluidremoval is desired. Well known algorithms such as PI and PID regulatorscan be employed using deviation of the SvO₂ measurement from baseline asinput and the speed of ultrafiltrate pump as the output.

[0063]FIG. 7 illustrates the electrical architecture of theultrafiltration controller system 600 (110 in FIG. 1), showing thevarious signal inputs and actuator outputs to the controller. Theuser-operator inputs the desired ultrafiltrate extraction rate into thecontroller by pressing buttons on a membrane interface keypad 609 on thecontroller. Other user settings may include the maximum flow rate ofblood through the system, maximum time for running the circuit to filterthe blood, the maximum ultrafiltrate rate the maximum allowed deviationof the venous blood oxygen saturation from the baseline. The settingsinput by the user are stored in a memory and read and displayed by thecontroller CPU 605 (central processing unit, e.g., microprocessor ormicro-controller) on the display 610.

[0064] The controller CPU regulates the pump speeds by commanding amotor controller 602 to set the rotational speed of the blood pump 108to a certain speed specified by the controller CPU. Similarly, the motorcontroller adjusts the speed of the ultrafiltrate pump 114 in responseto commands from the controller CPU and to provide a particular filtrateflow velocity specified by the controller CPU.

[0065] Feedback signals from the pressure transducer sensors 611 areconverted from analog voltage levels to digital signals in an A/Dconverter 616. The digital pressure signals are provided to thecontroller CPU as feedback signals and compared to the intended pressurelevels determined by the CPU. In addition, the digital pressure signalsmay be displayed by the monitor CPU 614.

[0066] The motor controller 602 controls the velocity, rotational speedof the blood and filtrate pump motors 603, 604. Encoders 607 and 606mounted to the rotational shaft of each of the motors as feedbackprovide quadrature signals (e.g., a pair of identical cyclical digitalsignals, but 60° out-of-phase with one another). These signal pairs arefed to a quadrature counter within the motor controller 602 to give bothdirection and position. The direction is determined by the signal leadof the quadrature signals. The position of the motor is determined bythe accumulation of pulse edges. Actual motor velocity is computed bythe motor controller as the rate of change of position. The controllercalculates a position trajectory that dictates where the motor must beat a given time and the difference between the actual position and thedesired position is used as feedback for the motor controller. The motorcontroller then modulates the percentage of the on time of the PWMsignal sent to the one-half 618 bridge circuit to minimize the error. Aseparate quadrature counter 617 is independently read by the ControllerCPU to ensure that the Motor Controller is correctly controlling thevelocity of the motor. This is achieved by differentiating the change inposition of the motor over time.

[0067] The monitoring CPU 614 provides a safety check that independentlymonitors each of the critical signals, including signals indicative ofblood leaks, pressures in blood circuit, weight of filtrate bag, motorcurrents, air in blood line detector and motor speed/position. Themonitoring CPU has stored in its memory safety and alarm levels forvarious operating conditions of the ultrafiltrate system. By comparingthese allowable preset levels to the real-time operating signals, themonitoring CPU can determine whether a safety alarm should be issued,and has the ability to independently stop both motors and reset themotor controller and controller CPU if necessary.

[0068] Input from the Oxygen sensor 615 is converted to a digital signalsimilar to other analog signals. Alternatively, if a microprocessorbased sensor is used, it can be already in a digital for. This signalinput allows CPU 605 to recalculated the desired ultrafiltration rateand control the rotational speed of the pump 114 to prevent reduction inthe patient's cardiac output and hypotension without help from theoperator.

[0069] The preferred embodiment of the invention now known to theinvention has been fully described here in sufficient detail such thatone of ordinary skill in the art is able to make and use the inventionusing no more than routine experimentation. The embodiments disclosedherein are not all of the possible embodiments of the invention. Otherembodiments of the invention that are within the sprite and scope of theclaims are also covered by this patent.

What is claimed is:
 1. A method for preventing hypotension in a mammalian patent whose blood is being withdrawn, treated in a blood treatment device of an extracorporeal blood circuit for removal of fluid, and infused into the patient, said method comprising the steps of: a. monitoring oxygen concentration in blood flowing through the circuit, and b. adjusting a flow rate of ultrafiltrate extracted from blood if the oxygen concentration in blood varies from a predetermined target value.
 2. A method for preventing hypotension as in claim 1 wherein the oxygen concentration is a mixed venous oxygen saturation (SvO₂) level.
 3. A method for preventing hypotension as in claim 1 wherein the oxygen concentration is a venous oxygen saturation (SvO₂) level of blood taken from a peripheral vein.
 4. A method as in claim 1 where oxygen concentration is measured at a blood withdrawal tube of the extracorporeal circulation circuit between a patient connection and a blood pump
 5. A method for preventing hypotension as in claim 2 wherein the target value is the sum of an oxygen concentration level determined during an initial phase of treating the blood in the circuit and a predetermined oxygen change value.
 6. A method for preventing hypotension as in claim 5 wherein the predetermined change value is selected by an operator.
 7. A method for preventing hypotension as in claim 5 wherein the predetermined change value is no greater than a seven percent difference than the determined initial oxygen saturation level.
 8. A method for preventing hypotension as in claim 1 wherein the target value is preprogrammed in a controller for the circuit.
 9. A method for preventing hypotension as in claim 1 wherein the oxygen concentration is determined using an optical biosensor.
 10. A method for preventing hypotension as in claim 1 wherein the oxygen concentration is applied to estimate cardiac output and, in step b, reducing filtration if the estimated cardiac output falls a predetermined amount.
 11. A method for preventing hypotension as in claim 1 wherein the oxygen concentration is relative to an initial oxygen concentration level.
 12. A method for preventing hypotension as in claim 1 wherein the oxygen concentration is an oxygen concentration of blood in the circuit.
 13. A method of controlling an extracorporeal blood circuit comprising the steps of: a. withdrawing blood from a withdrawal blood vessel in a patient into the extracorporeal circuit; b. filtering fluids from blood flowing through the circuit at a controlled filtration rate; c. estimating a cardiac output level of the patient; d. reducing the filtration flow rate if the measured cardiac output falls below a threshold level.
 14. A method of controlling an extracorporeal blood circuit as in claim 13 wherein the cardiac output level is determined by monitoring oxygen level of the venous blood.
 15. A method of controlling an extracorporeal blood circuit as in claim 13 wherein the blood circuit includes an oxygen saturation sensor having an emitter and a receiver mounted on opposite sides of a bloodline of said circuit.
 16. A method of controlling an extracorporeal blood circuit as in claim 13 wherein the controlled filtration rate is reduced by temporarily stopping filtration.
 17. A method of controlling an extracorporeal blood circuit as in claim 13 wherein the controlled filtration rate is reduced by slowing an ultrafiltration pump.
 18. A method of controlling an extracorporeal blood circuit as in claim 13 wherein the controlled filtration rate is determined by cyclically starting and stopping the filtration of fluids in accordance with a duty cycle, and the filtration rate is reduced by reducing an OFF period of the duty cycle.
 19. A system for treating blood from a patient comprising: an extracorporeal circuit having a blood passage including a blood withdrawal tube, a filter and an infusion tube, said filter having filter blood passage in fluid communication with the withdrawal tube, a blood outlet in fluid communication with the infusion tube, a filter membrane in fluid communication with the blood passage, a filter output section on a side of the membrane opposite to the blood passage, and a filtrate output line in fluid communication with the filter output section; a biosensor coupled to said extracorporeal circuit and generating a feedback signal indicative of cardiac output of the patient; a filtrate pump coupled to the filtrate output line and adapted to draw filtrate fluid from the filter at a controlled filtration rate, and a filtrate pump controller regulating the controlled filtration rate based on the feedback signal, wherein the pump controller includes a processor and a memory storing a control algorithm to determine whether a feedback signal threshold is exceeded by the feedback pressure signal, said controller reducing the controlled filtration if the feedback signal exceeds the feedback signal threshold.
 20. A system as in claim 19 wherein the feedback signal is indicative of an oxygen level in the venous blood.
 21. A system as in claim 19 wherein the feedback signal threshold is determined based on a sum of a feedback signal obtained during an initial phase of a treatment of the patient and a predetermined current feedback signal change.
 22. A system as in claim 19 wherein the filter is a hemofilter.
 23. A system as in claim 19 wherein the treatment device is a dialysis filter.
 24. A system as in claim 19 wherein the treatment device is an ultrafiltration filter. 